Maternal and neonatal outcomes in patients with hepatitis C and intrahepatic cholestasis of pregnancy: The sum of the parts.

OBJECTIVE: Hepatitis C virus and intrahepatic cholestasis of pregnancy (ICP) are well-known independent risk factors for adverse outcomes in pregnancy. In addition, it is well-established that there is an association between Hepatitis C and ICP. This study's objective was to describe the impact of having both Hepatitis C and ICP on maternal and obstetric outcomes compared to patients having either Hepatitis C or ICP. METHODS: We conducted a retrospective cohort study of the Nationwide Readmissions Database, an all-payor sample of discharges from approximately 60% of US hospitalizations. Deliveries at 24-42+ weeks between 10/2015 and 12/2020 were included. Diagnosis of Hepatitis C and ICP, and outcomes related to severe maternal morbidity were identified using International Classification of Disease-10 codes. Patients were categorized based on Hepatitis C and ICP status. Weighted logistic and negative binomial regression analyses were used to evaluate the association between Hepatitis C and ICP status and outcomes, adjusting for patient and hospital characteristics. The primary outcome was any severe maternal morbidity; secondary outcomes included acute respiratory distress syndrome, acute kidney injury, sepsis, gestational diabetes, cesarean delivery, preterm birth, and hospital length of stay. We modeled interaction terms between ICP and Hepatitis C to assess whether there was a greater or lesser effect from having both conditions on outcomes than we would expect from additive combination of the individual components (i.e., synergy or antagonism). RESULTS: A total of 10,040,850 deliveries between 24-42+ weeks were identified. Of these, 45,368 had Hepatitis C only; 84,582 had ICP only; and 1,967 had both Hepatitis C and ICP. Patients with both Hepatitis C and ICP had 1.5-fold higher odds of developing severe maternal morbidity compared to having neither. There was an also an increased odds of severe maternal morbidity in patients with both Hepatitis C and ICP compared to patients with only Hepatitis C or ICP. Having both was also associated with higher odds of preterm birth and length of stay compared to having only Hepatitis C, only ICP, or neither (preterm birth: aOR 5.09, 95% CI 4.87-5.33 vs. neither; length of stay: 46% mean increase, 95% CI 35-58% vs. neither). Associations were additive-no significant interactions between hepatitis C and cholestasis were found on rates of severe maternal morbidity, acute respiratory distress syndrome, acute kidney injury, sepsis, cesarean section, or preterm birth (all p>0.05), and was minimal for gestational diabetes and length of stay. CONCLUSION: Hepatitis C and ICP are independent, additive risk factors for adverse maternal and obstetric outcomes. Despite physiologic plausibility, no evidence of a synergistic effect of these two diagnoses on outcomes was noted. These data may be useful in counseling patients regarding their increased risk of adverse outcomes when ICP presents in association with Hepatitis C versus ICP alone.

Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with a 4- to 10-fold increase in the risk of stillbirth in the absence of intervention, leading to recommendations for antenatal assessment, ursodiol use, and often preterm or early term delivery. OBJECTIVE: This study aimed to determine whether current management strategies for intrahepatic cholestasis of pregnancy mitigate the elevated risk of stillbirth at a population level. STUDY DESIGN: This was a retrospective cohort study using the 2015-2020 National Readmissions Database, an administrative database developed by the United States Agency for Healthcare Research and Quality. Our study identified delivery hospitalizations, gestational age at delivery, occurrence of intrahepatic cholestasis of pregnancy and stillbirth, and comorbid conditions using the International Classification of Diseases diagnosis and procedure codes. Moreover, this study compared the timing of delivery and stillbirth rates of pregnant patients with intrahepatic cholestasis of pregnancy vs those without intrahepatic cholestasis of pregnancy at the time of delivery hospitalization. RESULTS: This study identified a cohort of 9,987,705 delivery hospitalizations in the National Readmissions Database, corresponding to a weighted national estimate of 18,609,207 births. Of these births, 152,040 (0.8%) were noted to have an intrahepatic cholestasis of pregnancy diagnosis. Patients with an intrahepatic cholestasis of pregnancy diagnosis were older, with small differences in comorbidities, such as a higher rate of gestational diabetes mellitus, than patients without an intrahepatic cholestasis of pregnancy diagnosis at delivery hospitalization. The overall rates of stillbirth were lower among those with intrahepatic cholestasis of pregnancy than among those without intrahepatic cholestasis of pregnancy (252 vs 386 per 100,000 deliveries; risk difference, 133 fewer per 100,000 deliveries; 95% confidence interval, 98-170), a finding that persisted after adjustment for insurance status, socioeconomic factors, and comorbid conditions (risk difference, 160 fewer stillbirths per 100,000 deliveries; 95% confidence interval, 127-194). Furthermore, although patients with intrahepatic cholestasis of pregnancy were more likely to deliver before term than those without intrahepatic cholestasis of pregnancy (30.1% vs 9.3%; P<.001), increased rates of stillbirth were not noted at any point after stratification of the cohort by gestational age at delivery. CONCLUSION: Patients with intrahepatic cholestasis of pregnancy diagnosis codes delivered earlier than those without intrahepatic cholestasis of pregnancy diagnosis codes, but the percentage of births affected by stillbirth was lower, even when stratifying for gestational age at birth. These results may provide reassurance to patients receiving an intrahepatic cholestasis of pregnancy diagnosis that current management does mitigate stillbirth risk in intrahepatic cholestasis of pregnancy.

The relationship between maternal anemia and electronic fetal monitoring patterns.

BACKGROUND: Anemia is a commonly diagnosed comorbidity in pregnancy that is associated with increased risk of maternal and neonatal complications. Recent data demonstrate that maternal anemia is associated with higher umbilical artery and umbilical vein O2 content at the time of delivery. OBJECTIVE: This study aimed to examine the relationship between maternal anemia and electronic fetal monitoring patterns associated with fetal hypoxia. STUDY DESIGN: This is a secondary analysis of a prospective cohort study of singleton term deliveries with cord gases and universal complete blood count collected on admission between 2010 and 2014. Maternal anemia was defined as hemoglobin ≤11.0 g/dL on admission. The primary outcome was a composite of high-risk category 2 electronic fetal monitoring features in the last 60 minutes before delivery (recurrent late and/or variable decelerations, minimal variability, tachycardia, or >1 prolonged deceleration); secondary outcomes were total deceleration area and total deceleration area >90th percentile. Of the 8580 patients in the original study, 8196 were included in the analysis. Outcomes were compared between patients with and without anemia. Multivariable logistic regression was used to adjust for potentially confounding factors, including hypertensive disorders of pregnancy and induction of labor. RESULTS: Of the 8196 patients with complete blood count on admission and fetal monitoring data, 2672 (32.6%; 2672/8196) were anemic and 5524 (67.4%; 5524/8196) were not. Patients with anemia were significantly less likely to have composite high-risk category 2 features on electronic fetal monitoring (34.2% vs 32.0%; adjusted risk ratio, 0.93; 95% confidence interval, 0.86-0.99). Women with anemia also had decreased total deceleration area and were less likely to have total deceleration area >90th percentile (18.7% vs 16.2%; adjusted risk ratio, 0.85; 95% confidence interval, 0.77-0.94). CONCLUSION: Patients with anemia are less likely to have high-risk category 2 electronic fetal monitoring features associated with fetal hypoxia. This finding is consistent with the association between maternal anemia and increased umbilical cord O2 content, and suggests that maternal anemia may be protective against intrapartum fetal hypoxia.

The impact of physical activity during pregnancy on labor and delivery.

BACKGROUND: Physical activity in pregnancy is associated with decreased risks of adverse pregnancy outcomes such as gestational diabetes and preeclampsia. However, the relationship between the amount and type of physical activity during pregnancy and subsequent labor outcomes remains unclear. OBJECTIVE: This study aimed to test the hypothesis that higher levels of physical activity across different lifestyle domains in pregnancy are associated with a shorter duration of labor. STUDY DESIGN: This study is a secondary analysis of a prospective cohort study in which patients with singleton pregnancies without a major fetal anomaly were administered the Kaiser Physical Activity Survey in each trimester. The Kaiser Physical Activity Survey was designed specifically to quantify various types of physical activities in women and includes 4 summative indices-housework/caregiving, active living habits, sports, and occupation. The study included women at full-term gestations admitted for induction of labor or spontaneous labor. The primary outcome of this analysis was duration of the second stage of labor. Secondary outcomes were duration of the active stage, prolonged first and second stage, mode of delivery, rates of second-stage cesarean delivery, operative vaginal delivery, severe perineal lacerations, and postpartum hemorrhage. These outcomes were compared between patients with and without high physical activity levels, defined as overall Kaiser Physical Activity Survey score ≥75th percentile in the third trimester. Multivariable logistic regression was used to adjust for obesity and epidural use. In addition, a subgroup analysis of nulliparous patients was performed. RESULTS: A total of 811 patients with complete Kaiser Physical Activity Survey data in the third trimester were included in this analysis. The median Kaiser Physical Activity Survey score was 9.5 (8.2-10.8). Of the 811 patients, 203 (25%) had higher levels of physical activity in pregnancy. There was no difference in the duration of the second stage of labor between patients with and without higher physical activity levels (1.29±2.94 vs 0.97±2.08 hours; P=.15). The duration of active labor was significantly shorter in patients with higher levels of physical activity (5.77±4.97 vs 7.43±6.29 hours; P=.01). Patients with higher physical activity levels were significantly less likely to have a prolonged first stage (9.8% vs 19.4%; P<.01; adjusted relative risk, 0.55; 95% confidence interval, 0.34-0.83). However, rates of prolonged second-stage cesarean delivery, operative vaginal deliveries, and perineal lacerations were similar between the 2 groups. CONCLUSION: Patients who are more physically active during pregnancy have a shorter duration of active labor.

The relationship between maternal anemia and umbilical cord oxygen content at delivery.

BACKGROUND: Anemia is one of the most commonly diagnosed comorbidities in pregnancy and is known to increase the risk of obstetrical complications. However, little is known about the effect of anemia on placental oxygen transfer and fetal oxygenation. OBJECTIVE: This study examined the relationship between maternal anemia and fetal oxygenation status at delivery as measured by umbilical cord partial pressure of oxygen. STUDY DESIGN: This is a secondary analysis of a prospective cohort study of singleton term deliveries with universal admission complete blood count and umbilical cord gases between 2010 and 2014. Maternal anemia was defined as hemoglobin of ≤10 g/dL on admission. The primary outcomes were umbilical artery and vein partial pressure of oxygen; the secondary outcomes were acidemia (umbilical artery pH of <7.1), hypoxemia (umbilical artery or umbilical vein partial pressure of oxygen at the <5th percentile), and hyperoxemia (umbilical artery/umbilical vein partial pressure of oxygen at the >90th percentile). Outcomes were compared between patients with and without anemia. RESULTS: Maternal anemia was associated with a significantly higher umbilical artery partial pressure of oxygen (median [interquartile range], 20 [16-24] vs 19 [15-24] mm Hg; P=.01) and umbilical vein partial pressure of oxygen (median [interquartile range], 30 [25-36] vs 29 [23-34] mm Hg; P<.01). Neonates born to anemic mothers were more likely to have umbilical vein hyperoxemia (15.7% vs 10.9%; adjusted odds ratio, 1.51; 95% confidence interval, 1.26-1.81) with no difference in umbilical artery hyperoxemia. There was no difference in the rates of umbilical artery or umbilical vein hypoxemia. Although maternal anemia was associated with a significant difference in umbilical artery pH (7.28±0.060 vs 7.27±0.065; P<.01), there was no difference in the rate of neonatal acidemia between groups (1.6% vs 1.9%; adjusted odds ratio, 0.93; 95% confidence interval, 0.55-1.55). CONCLUSION: Umbilical cord oxygen content is higher in anemic mothers. Maternal anemia may lead to adaptations in maternal, placental, and fetal physiology, allowing for easier unloading of oxygen to the placenta and increased oxygen transfer to the fetus.

The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content.

BACKGROUND: Maternal oxygen (O2) administration is a commonly performed intrauterine resuscitation technique though to improve fetal oxygenation. However, hyperoxygenation is known to be harmful in both neonates and adults. Currently, there are no formal recommendations on whether a certain dose or duration of O2 may be most helpful in improving umbilical cord gases or neonatal outcomes. OBJECTIVE: We tested the hypothesis that prolonged supplemental O2 exposure during labor is associated with increased umbilical cord O2 concentrations. STUDY DESIGN: This was a planned secondary analysis of a randomized noninferiority trial comparing O2 with room air in laboring patients. Patients were randomized to receive either 10 L/min O2 or room air at any point during active labor when they developed a category II fetal heart tracing that would otherwise require resuscitation. The primary outcome variable for this analysis was partial pressure of O2 in the umbilical vein. The secondary outcome variable was partial pressure of O2 in the umbilical artery. These outcome variables were compared between patients with short durations of O2 exposure and those with long durations of O2 exposure, defined as <75th percentile and ≥75th percentile of duration, respectively. The outcomes were also compared among the groups that received room air, O2 for short durations, and O2 for long durations. RESULTS: Among the 99 patients with paired and validated cord gases who were included in this analysis, the partial pressure of O2 in the umbilical vein was significantly lower in patients who received O2 supplementation for longer durations than in those who received O2 for shorter durations (median interquartile range 25.5 [21.5-33] vs 32.5 [26.5-37.5] mm Hg; P<.03). There was no difference in the partial pressure of O2 in the umbilical artery or other cord gases between the short and long duration O2 supplementation groups. Other methods of intrauterine resuscitation were similar between the short and long duration O2 supplementation groups. There was no difference in the partial pressure of O2 in the umbilical artery or in the umbilical vein when the room air, short duration O2 supplementation, and long duration O2 supplementation groups were compared. CONCLUSION: Longer durations of O2 exposure are not associated with a higher partial pressure of O2 in the umbilical cord. In fact, patients with longer durations of O2 exposure had lower partial pressure of O2 in the umbilical vein, suggesting impaired placental O2 transfer with prolonged O2 exposure.